Since the etiology of most cases of hypertension is unknown, the search for effective antihypertensive agents is largely empirical, and various classes of agents are currently employed for general antihypertensive therapy.
While a number of effective agents exist, because of the significant, adverse side-effects produced by all effective antihypertensive agents, and because of the frequent need to periodically change agents, the search for additional agents continues.
Various derivatives of adenosine and adenine have been reported to exhibit various pharmaceutical activities, i.e., antiviral activity, blood cholesterol lowering activity and cardiovascular activities. In the cardiovascular field, the adenosine derivatives have variously been reported to be useful as coronary dilators useful for treating angina pectoris, coronary insufficiency and myocardial infarct, and as blood platelet aggregate inhibitors.
N.sup.6 -substitution has been reported to produce adenosine derivatives which are useful as antihypertensive agents. See for example CA82:32 C(1957); CA83:71866m(1975); CA82:17136 (1975). N.sup.6 -substitution has also produced agents which exhibit widely varying activities, i.e., coronary dilating and blood platelet aggregration inhibitory activities (CA81:78193g(1974)); antipolytic and antihypercholesteremic activity (CA84:150915a(1976)); anti-tumor activity (Current Abstracts of Chemistry, 58, issue 605, 231440(1975); growth promoting activity (CA76:55126v(1972).
N.sup.6 -adenosine derivatives have been reported to act on the heart and blood circulation, especially on coronary circulation (NE68,12083) and N.sup.6 -.beta.-naphthyl and aralkyl, phenyl and benzyl-substituted adenosines have been reported to exhibit coronary dilating and blood platelet aggregation-inhibiting activities.
The present invention provides N.sup.6 -(2-hydroxypropyl)aryl-substituted adenosines and adenines which are potent antihypertensive agents. This activity is wholly surprising because of the widely varying utilities of N.sup.6 -substituted adenosines and adenines.